Di Matteo V, Di Mascio M, Di Giovanni G, Esposito E
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Chieti, Italy.
Psychopharmacology (Berl). 2000 May;150(1):45-51. doi: 10.1007/s002130000420.
Previous studies of conventional tricyclic and non-tricyclic antidepressants have suggested that a number of these drugs display considerable pharmacological activity at 5-HT2C receptors in the brain. There is evidence that 5-HT2C receptors are involved in the control of the activity of the central dopaminergic system. Therefore, the effects of amitriptyline (5 mg/kg and 10 mg/kg i.p.) and of the atypical antidepressant mianserin (2.5 mg/kg and 5 mg/kg i.p.) were studied on the extracellular concentration of dopamine (DA) in the nucleus accumbens of chloral hydrate-anesthetized rats, using intracerebral microdialysis. Amitriptyline and mianserin significantly increased DA release (+31.1 +/- 7.9% and +33.6 +/- 4.3%, respectively) at the higher doses. In addition, lower doses of mianserin (2.5 mg/kg i.p.) and amitriptyline (5 mg/kg i.p.) blocked the inhibitory action of RO 60-0175 (1 mg/kg i.p.), a selective 5-HT2C receptor agonist, on DA release. The effect of RO 60-0175 (1 mg/kg i.p.) was completely blocked by SB 242084 (2.5 mg/kg i.p.), a selective and powerful 5-HT2C receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the nucleus accumbens by blocking 5-HT2C receptors.
以往对传统三环类和非三环类抗抑郁药的研究表明，其中许多药物在大脑中的5-羟色胺2C（5-HT2C）受体上表现出相当强的药理活性。有证据表明，5-HT2C受体参与中枢多巴胺能系统活动的控制。因此，采用脑内微透析技术，研究了阿米替林（腹腔注射5毫克/千克和10毫克/千克）和非典型抗抑郁药米安色林（腹腔注射2.5毫克/千克和5毫克/千克）对水合氯醛麻醉大鼠伏隔核中多巴胺（DA）细胞外浓度的影响。在较高剂量下，阿米替林和米安色林显著增加了DA释放（分别增加了+31.1±7.9%和+33.6±4.3%）。此外，较低剂量的米安色林（腹腔注射2.5毫克/千克）和阿米替林（腹腔注射5毫克/千克）阻断了选择性5-HT2C受体激动剂RO 60-0175（腹腔注射1毫克/千克）对DA释放的抑制作用。选择性强效5-HT2C受体拮抗剂SB 242084（腹腔注射2.5毫克/千克）完全阻断了RO 60-0175（腹腔注射1毫克/千克）的作用。综上所述，这些数据表明，阿米替林和米安色林通过阻断5-HT2C受体增加伏隔核中的DA释放。
